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Journal Details
Format
Journal
eISSN
1875-855X
First Published
01 Jun 2007
Publication timeframe
6 times per year
Languages
English

Search

Volume 6 (2012): Issue 3 (June 2012)

Journal Details
Format
Journal
eISSN
1875-855X
First Published
01 Jun 2007
Publication timeframe
6 times per year
Languages
English

Search

0 Articles

Editorial

Open Access

Can we do better at registering clinical trials?

Published Online: 04 Feb 2017
Page range: 333 - 335

Abstract

Original article

Open Access

Association of interleukin-10 polymorphism and malarial susceptibility in Pakistani population

Published Online: 04 Feb 2017
Page range: 337 - 342

Abstract

Abstract

Background: Malaria is a leading cause of morbidity and mortality worldwide resulting in approximately 350 to 500 million clinical cases and up to two million deaths. In Pakistan, 1.5 million cases of malaria are reported annually. The genetic factors of both host and pathogen are related to the severity of the disease. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that can play a key role in plasmodium falciparum infection. Variations in IL-10 production are genetically related to polymorphisms within the IL-10 promoter region.

Objective:We investigated the association of IL-10 gene promoter -1082 G/A, -819 C/T, and -592 C/A polymorphism with malarial susceptibility in Pakistani individuals.

Methods: Ninety malarial patients and 99 healthy control subjects were enrolled. IL-10 genotyping was performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Results: There was no significant difference observed in inheritance pattern of studied single nucleotide polymorphisms. All the alleles, genotypes, and haplotypes had almost similar frequencies among diseased and healthy control groups. IL-10 -1,082 homozygous G was comparatively higher in healthy subjects but difference was not statistically significant.

Conclusion: We have found no significant association between IL-10 promoter polymorphism and plasmodium falciparum infection in Pakistan. Our result from Pakistani population confirm previous association in studies from Thailand, Gambia, Republic of Mali, Tanzania, and contradict one from Kenyan population.

Keywords

  • IL-10
  • malaria
  • polymorphism
  • susceptibility
Open Access

Effect of nicotine on the release of lactate dehydrogenase and the production of tumor necrosis factor-α of cultured macrophage

Published Online: 04 Feb 2017
Page range: 343 - 350

Abstract

Abstract

Background: Nicotine can affect the development of Atherosclerosis (AS). Monocytes/macrophages are the important cells hi the AS lesions.

Objective: We studied the mechanisms of smoking on AS. The effects of nicotine on macrophage were investigated hi this study.

Methods: Different concentration of nicotine (6 × 10-9~-5 mol/L), different incubation time (3, 6, 9, 12, 18, and 24 horn s) and 7 β-hydroxycholesterol (50 μg ml) were schemed in this study. After exposure of macrophage to those different conditions, lactate dehydrogenase (LDH) activity and tumor necrosis factor-⃞ (TNF-α) content in the supernatant were assayed.

Results: Nicotine (6 × 10-9mol/L~-6×10-5mol/L) treatment resulted in a marked reduction of LDH in the supernatant (131,0±9.6 U/L. 129.7±6.2 U/L, 129.4±5.3 U/L, 134.2±8.4 U/L, and 138.3+9.7 U/L vs. 151.3+8.1 U/L, p <0.05 respectively, q-test). The same change trend was seen when co-treated with 7β-hydroxycholestrol and nicotine (135.7±7.6U/L, 135.6±6.6U/L, 136.1±6.7 U/L, 142.9±4.5 U/L, and 146.4±4.4 U/L vs. 152.4⃞6.2U/L, P<0.05 respectively, q-test). The peak effects occurred at the nicotine concentration of 6 × 10-7mol/L and the first 18-hours incubation. Nicotine (6 ×10-9mol/L~6 × 10-6mol L) treatment result in the increase of TNF-α in the supernatant (0.28±0.06 ng/mL, 0.32±0.05 ng/mL, 0.40±0.07 ng/mL. and 0.30±0.08 ng/mL vs. 0.17±0.05 ng/mL, p <0.05 respectively, q-test). Nicotine (6 × 10-5mol/L) treatment have no significant hicrease compared to the control group (0.21±0.08 ng/mL vs. 0.17+0.05 ng/mL, p >0.05, q-test). The peak effects occurred at the nicothie concentration of 6 × 10-7mol/L.

Conclusions: Nicotine can produce the beneficial effect on macrophage. Nicotine treatment can activate macrophage to produce TNF-α. Thus, nicotine can be a mechanism on the development of atherosclerosis.

Keywords

  • Lactate dehydrogenase
  • macrophage
  • nicotine
  • tumor necrosis factor-α
Open Access

Imatinib regulates the alternative pre-mRNA splicing of Bcl-x in K562 cells

Published Online: 04 Feb 2017
Page range: 351 - 359

Abstract

Abstract

Background: The alternative splicing of Bcl-x generates the proapoptotic Bcl-xs protein and the antiapoptotic variant Bcl-xl. Previous studies have demonstrated that some chemotherapeutic agents such as emetine, staurosporine, and epigallocatechin gallate (EGCG) in combination with ibuprofen significantly altered the ratio of the Bcl-x variants Bcl-xs/Bcl-xl in various cell lines, suggesting Bcl-x splicing might be affected by the exogenous stimuli.

Objective: We investigated the regulative role of imatinib in the alternative pre-mRNA splicing of Bcl-x in K562 cells and the related mechanism.

Methods: Cell proliferation was measured using WST assay kit. Cell apoptosis was assayed using an Annexin V-FITC Apoptosis Detection Kit. RT-PCR and western blot assay was used to analyze the mRNA and protein level of alternative splicing of exon 2 in the Bcl-x gene respectively.

Results: Imatinib regulated the alternative splicing in the Bcl-x gene in the K562 cells. In addition, we found that hydroxyurea, another agent for the therapy of CML, could enhance the effect of imatinib on the ratio of the Bcl-xl/Bcl-xs. Moreover, the induction of alternative splicing was correlated with protein phosphatase 1 (PP1). Alternatively, pretreatment with calyculin efficiently blocked imatinib-induced alternative splcing in the K562 cells compared with okadaic acid, which showed an important role of PP1 in regulating imatinib-induced splicing.

Conclusion: Imatinib regulates the alternative splicing of Bcl-x in K562 cells, which may be associated with the activation of PP1.

Keywords

  • Alternative splcing
  • Bcl-x
  • chronic myelogenous leukemia
  • imatinib
  • protein phosphatase 1
Open Access

Percutaneous ipsilateral portal vein embolization using histoacryl glue: changing LR, resectibility rate and complications

Published Online: 04 Feb 2017
Page range: 361 - 367

Abstract

Abstract

Background: Liver resection has been the main strategy for treating either primary or secondary liver cancer. However, major liver resection may lead to postoperative liver failure. Portal vein embolization (PVE) is a procedure to induce hypertrophy of a liver remnant (LR) before major resection surgery. There are many variations in procedural techniques, with different advantages and disadvantages.

Objective: We studied change in liver remnant volume, resectibility rate, and complications after percutaneous ipsilateral portal vein embolization (PVE) using histoacryl glue.

Methods: Clinical data of 25 patients who underwent ipsilateral PVE were reviewed. Eighteen patients who had pre- and post- CT studies had total liver volumes (TLV) and LR volumes determined before and after the procedure using MDCT volumetry. Complications and respectability rates were recorded.

Results: All 18 patients who had pre-CT and post-CT studies had increased LR volumes. The mean of LR volumes before and after ipsilateral PVE were calculated at about 449 ml and 586 ml, which were statistically significant (p <0.001). The mean enlargement of LR was 30% (range 4 to 120%). There were no deaths or serious complications. The resectabilty rate was 76%.

Conclusion: Percutaneous transhepatic ipsilateral PVE could increase the LR volumes before major hepatic resection. There were no significant complications in our study group.

Keywords

  • Histoacryl glue
  • ipsilateral approach
  • liver cancer treatment
  • liver remnant
  • portal vein embolization
Open Access

Elevated adiponectin is associated with poor outcome in children with biliary atresia

Published Online: 04 Feb 2017
Page range: 369 - 376

Abstract

Abstract

Background: Biliary atresia (BA) is a severe neonatal liver disease characterized by progressive fibrosclerotic obliteration of the extrahepatic biliary tree.

Objective: We compared serum adiponectin in post Kasai BA patients with healthy controls and associate adiponectin with clinical outcomes of BA patients.

Methods: One hundred and six postoperative BA patients and 40 controls were recruited in this study. BA patients were categorized into two groups based on their serum total bilirubin (TB) levels (TB<2 mg/dL, no jaundice vs. TB ≥2 mg/dL, persistent jaundice) and alanine aminotransferase (ALT) levels (ALT<45 IU/L, normal ALT vs. ALT ≥45 IU/L, elevated ALT). Serum adiponectin levels were determined by enzyme-linked immunosorbent assay.

Results: BA patients had higher serum adiponectin levels than healthy controls (172.8±90.9 vs. 93.9±53.5 ng/mL, p <0.001). Serum adiponectin levels were elevated in BA patients with jaundice compared to those without jaundice (229.6±89.0 vs. 139.7±74.5 ng/mL, p <0.001). Furthermore, BA patients with elevated ALT displayed significantly higher levels of serum adiponectin than those with normal ALT (187.2±91.8 vs. 117.6±62.8 ng/mL, p <0.001). Additionally, BA patients with portal hypertension had substantially higher serum adiponectin than those without portal hypertension and a poorer clinical outcome (207.0±90.2 vs. 118.5±62.1 ng/mL, p <0.001).

Conclusions: Increased serum adiponectin was associated with a poor outcome in postoperative BA patients. Serum adiponectin might be utilized as a biochemical indicator reflecting the deterioration of liver function and poorer outcome in BA after Kasai operation.

Keywords

  • Adiponectin
  • biliary atresia
  • jaundice
  • liver fibrosis
  • portal hypertension
Open Access

Antiosteoporotic effect of sequential extracts and freezedried juice of Cissus quadrangularis L. in ovariectomized mice

Published Online: 04 Feb 2017
Page range: 377 - 384

Abstract

Abstract

Background: Osteoporosis becomes a major health problem in aging populations, and this disease increases the risk of bone fractures, leading to disability and mortality. Cissus quadrangularis L. (CQ) has been reported to have beneficial effects on bone metabolism; however, there has been no investigation to identify the active compounds responsible for this activity.

Objective: Sequential extracts (hexane, dichloromethane, ethanol, and water) and freeze-dried CQ juice were investigated to determine their effects on bone metabolism in an ovariectomized (ovx) mouse model.

Methods: Six-week-old ICR mice were divided into eight groups: sham-operated, ovx-control, estradiol (E2)- treated and five CQ-treated ovx-mouse groups (n = 3). The CQ extracts were orally administered at a dose equivalent to 5g of crude powder/kg/day for 8 weeks. Bone mineral densities (BMD) of the femur and tibia, serum levels of osteocalcin (bone formation marker) and TRAP5b (bone resorption marker), and histomorphological change of lumbar spine were determined at the end of the experiment.

Results: The BMD of the femur and tibia in the hexane-treated group were elevated to the same level as those of sham-operated group. This BMDs correlated with restoration of the trabecular bone of the lumbar spine, which was only observed in the hexane-treated group. These results were also supported by the lowest serum levels of osteocalcin and TRAP5b observed in this group, compared to the ovx-control and E2-treated groups, representing a decrease in the bone turnover rate. Neither signs of abnormality nor pathological changes of internal organs were observed after the experiment.

Conclusion: The hexane extract possessed antiosteoporotic activity in ovariectomized mice without any toxicity throughout the experiment. Therefore, the hexane extract is the most interesting for further bioassay-guided purification of pharmacologically active compounds.

Keywords

  • Bone mineral density
  • medicinal plant
  • osteocalcin
  • osteoporosis
  • TRAP5b
  • Vitaceae
Open Access

Altered phosphorylation of mitogen-activated protein kinases in dorsal root ganglia and sciatic nerve of rats with cisplatin-induced neuropathy

Published Online: 04 Feb 2017
Page range: 397 - 411

Abstract

Abstract

Background: Peripheral neuropathy is a major side effect of cisplatin. Cisplatin preferentially accumulates in the dorsal root ganglia (DRG) and causes neuronal apoptosis. In vitro studies have implicated mitogenactivated protein kinases (MAPKs) in cisplatin-induced apoptosis. However, this has not been confirmed in vivo.

Objective: We studied the phosphorylation of MAPKs, ERK, JNK, and p38, in the DRG and sciatic nerve of rats treated with cisplatin, and correlated it with the neuropathic abnormalities.

Methods: Cisplatin 2 mg/kg was intraperitoneally injected in rats twice a week for five consecutive weeks. Neuropathy was assessed by measuring hind-paw thermal and mechanical thresholds, sciatic motor nerve conduction velocity (MNCV) and morphometric evaluation of DRG and sciatic nerve at various time points after the start of cisplatin treatment. Western blot analysis was done to determine the ratio of phosphorylated to total forms of MAPKs in the DRG and sciatic nerve.

Results: Cisplatin induced transient thermal hypoalgesia, late reduction in MNCV and histopathological abnormalities of DRG and sciatic nerve indicating the neuropathy. ERK was activated in the nerve and DRG in the eighth and twelfth weeks, respectively. Transient activation of JNK in the nerve and DRG was observed only in the first week. At the same time point to JNK, p38 was temporarily inhibited in the DRG. Late activation of ERK was correlated with the presence of pathological changes, suggesting the possible role of ERK in these abnormalities. No correlation between MAPKs and functional abnormalities was observed.

Conclusion: MAPK ERK might play a role in cisplatin-induced structural alterations in the DRG and sciatic nerve and can be the therapeutic target. However, to prove this hypothesis, future studies using the ERK inhibitor must be done.

Keywords

  • Cisplatin
  • dorsal root ganglia
  • MAPK
  • neuropathy
  • sciatic nerve
Open Access

Effect of xanthoxylin on melanin content and melanogenic protein expression in B16F10 melanoma

Published Online: 04 Feb 2017
Page range: 413 - 422

Abstract

Abstract

Background: Reduced production of melanin and decreased or absence of melanocytes leads to various hypopigmentation disorders. Melanin synthesis is regulated by melanogenic proteins such as tyrosinase, tyrosinase-related protein 1 (TRP-1) and tyrosinase-related protein 2 (TRP -2), as well as their transcription factors.

Objectives: This study elucidated the effects of xanthoxylin on melanin content, dendriticity, melanogenic protein expression and its signal transduction pathways in mouse B16F10 melanoma cells (B16F10 cells).

Methods: Melanin production of B16F10 cells was measured by using a melanin content assay. The effect of xanthoxylin on the dendriticity of B16F10 cells was determined by a melanocyte dendricity assay. RT-PCR was used to investigate the effects of xanthoxylin on the melanogenic protein expression.

Results: We found that xanthoxylin increased melanin production, number of dendrites, tyrosinase, and microphthalmia-associated transcription factor (MITF) expression in cultured B16F10 cells. In addition, PKA and PKC inhibitor decreased melanin production, tyrosinase, and MITF expression in xanthoxylin-treated cells. However, xanthoxylin did not inhibit TRP-1 and TRP-2 expression.

Conclusion: These results indicated that xanthoxylin induces melanogenesis mainly via cAMP-mediated PKA activation. Other signaling pathways may also play a role in xanthoxylin-induced melanogenesis.

Keywords

  • Melanocyte
  • melanin
  • xanthoxylin

Brief communication (Original)

Open Access

Endorsement and implementation of high impact factor medical journals on the International Committee of Medical Journal Editors (ICMJE) policy of mandatory clinical trial registration

Published Online: 04 Feb 2017
Page range: 423 - 427

Abstract

Abstract

Objective: We determined the proportion of highest impact factor journals that follows the ICMJE policy of clinical trial registration and identified factors associated with policy implementation.

Study design and setting: Ten highest impact factor journals from ten specialties were identified from the 2009 Journal Citation Reports. Instructions for authors were reviewed for the statements regarding the trial registration. If the registration policy was mentioned in the instructions, the published articles were assessed to determine if the policy was actually implemented. The publishers, membership in Committee on Publication Ethics, journal vintage, etc., were analyzed for association with the policy implementation.

Results: Of 87 relevant journals, 58.6% endorsed the policy and 35.6% strictly implemented it. Factors for journals associated with strict clinical trial registration policy implementation were Internal Medicine specialty (OR 19.19; 95%CI: 2.21, 166.50; p = 0.007), ICMJE’s URM followers (OR 7.14; 95%CI: 2.62, 19.46; p <0.001), longer years of publication (OR for every 10 year 1.31; 95%CI: 1.16, 1.49; p = 0.001), and higher impact factors (OR for every 1 JIF 1.70; 95%CI: 1.25, 2.32; p = 0.001).

Conclusion: Only one third of the highest impact factor journals strictly implemented ICMJE policy. Associated factors were identified.

Keywords

  • Associated factors
  • clinical trial registration
  • endorsement
  • impact factor
  • implementation
  • policy
Open Access

Safety of equine rabies immunoglobulin injection into fingers and toes

Published Online: 04 Feb 2017
Page range: 429 - 432

Abstract

Abstract

Background: International guidelines recommend infiltration of Rabies Immunoglobulin (RIG) into and around animal bite wounds in category III potential rabies exposures. This is followed by vaccination with an approved tissue culture rabies vaccine.

Objective: We assessed the feasibility and safety of injecting Equine Rabies Immunoglobulin (ERIG) into anatomical sites with less space for expansion. Methods: A prospective study on 195 patients having category III animal bites over fingers, toes, nose, ear lobule, and eyelids was carried out at the Anti-Rabies Clinic of Maharaja Krushna Chandra Gajapati Medical College, Berhampur, Orissa, India. All patients received Equine Rabies Immunoglobulin (ERIG).

Results: No major side effects were observed. Minor side effects included induration (67.1%), pain (53.8%), and pruritus (29.2%). No compartment syndrome was seen.

Conclusion: Injecting ERIG into and around bite wounds following WHO and US-CDC guidelines in areas where no ample space is available, such as fingers, is a safe procedure.

Keywords

  • Equine rabies immunoglobulin
  • finger injury
  • rabies
Open Access

Endoplasmic reticulum protein ERp29 and doxorubicininduced toxicity in H9c2 cardiomyocytes: a comparative proteomics analysis

Published Online: 04 Feb 2017
Page range: 433 - 437

Abstract

Abstract

Background: Doxorubicin has been widely used to treat many cancers. It also induces cumulative and delayed cardiomyopathy. New biological markers to predict cardiac toxicity is needed.

Objectives: We identified novel markers and potential therapeutic targets of doxorubicin (DOX)-induced cardiac toxicity by proteomics approach.

Methods: The protein profiling of H9c2 cells in response to DOX at an apoptosis-induced concentration (0.5⃞M) were compared by two-dimensional electrophoresis (2-DE) and mass spectrometry.

Results: A total of nine differently expressed proteins were identified including six up-regulated and three downregulated proteins. We further confirmed the expression of two down-regulated proteins, prohibitin and endoplasmic reticulum protein ERp29 (ERp29), decreased in response to DOX induction by Western-blot, and over-expression of ERp29 also partially recovered the MTT reduction.

Conclusion: We first identified ERp29 and prohibitin as novel markers for DOX toxicity, and ERp29 might be a candidate target to develop novel therapeutic strategies to alleviate adverse effects of doxorubicin-based chemotherapies.

Keywords

  • Apoptosis
  • cardiac toxicity
  • doxorubicin
  • ERp29
  • proteomics
Open Access

The expression of opticin in vitreous body and retina of diabetes mellitus rats

Published Online: 04 Feb 2017
Page range: 439 - 444

Abstract

Abstract

Background: Diabetic retinopathy is a common complication of diabetes mellitus. Opcitin is a glycoprotein present in the vitreous body. Its role in diabetic retinopathy needs to be further defined.

Objective: Investigate and compare the mRNA and protein levels of opticin in vitreous body and retina in normal and diabetic rats.

Methods: Twenty-four male Sprague-Dawley (SD) rats were randomly divided into two groups (12/group), a streptozocin-induced diabetes (STZ) group and a control group. In the STZ group, 1% sterile STZ solution was injected into the rats intraperitonally (60mg/kg). An equal volume of sodium citrate buffer solution was administrated in the rats from the control group. The rats were sacrificed one month after various treatments. The eye bodies of three rats from each group were removed and fixed with 4% paraformaldehydeion for the following pathological analysis. Meanwhile, the vitreous bodies and retina of the other nine rats from each group were removed for the real-time PCR, immunohistochemistry, and western blot assays.

Results: The mRNA level of opticin in the vitreous body of diabetes mellitus (DM) rats was 5.66% of that of the control ones (p <0.01). The expression of opticin mRNA in retina of DM rats was 9.28% of that of the control ones (p <0.01). In addition, opticin protein was expressed in the vitreous body and retina of the normal rats, whereas it was negative in the DM ones.

Conclusions: The opticin expression in vitreous body and retina of diabetes rats was significantly decreased or even disappeared, which may suggest a key role of opticin in the development of diabetic retinopathy.

Keywords

  • Diabetic retinopathy
  • opticin
  • rat
Open Access

Acute cadmium exposure augments MMP-9 secretion and disturbs MMP-9/TIMP-1 balance

Published Online: 04 Feb 2017
Page range: 445 - 451

Abstract

Abstract

Background: Cadmium (Cd) is an extremely toxic metal commonly found in industrial work places, a food contaminant and a major component of cigarette smoke. Tobacco smoke and Cd inhalation result in alveolar inflammation, accumulation of immune cells and proteases/anti-proteases imbalance associated with chronic obstructive pulmonary disease and emphysema.

Objectives: We studied Cd toxicity on U-937 monocytoid cells and its influence on matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor (TIMP1) levels.

Methods: U-937 cells were cultured and treated with either concentrations of 1.0, 10.0 or 50.0 μM cadmium chloride. Cytotoxicity percentages were measured by activity assay of lactate dehydrogenase released into culture medium of treated and the control cells. MMP-9 and TIMP-1 levels were determined by ELISA. Zymography technique was used to quantify MMP-9 gelatinolytic activity in culture media of U-937 cells. Alterations in MMP-9 and TIMP-1 gene expressions in response to Cd were analyzed by real-time PCR method.

Results: Cd found to be dose-dependently cytotoxic where 50.0 μM Cd significantly increased LDH leakage from the cells (p <0.05). MMP-9 levels measured by ELISA and zymography methods showed significant 44% and 48% increase, respectively, following exposure to 50.0 μM of Cd (p <0.05). Cd doses did not exert any effect on TIMP-1 levels. Alteration in MMP-9/TIMP-1 genes expressions in response to Cd found to be below a half fold increase for all doses which were not statistically significant.

Conclusion: These results suggest that Cd has direct detrimental effects on cell viability, MMPs activity and protease/anti-protease balance which may contribute to alveolar wall destruction and pulmonary diseases.

Keywords

  • Cadmium
  • MMP-9
  • monocytic cells
  • TIMP-1
Open Access

TNF-α and G-CSF induce CD62L and CD106 expressions on rat bone marrow-derived MSCs

Published Online: 04 Feb 2017
Page range: 453 - 458

Abstract

Abstract

Background: Accumulating evidence suggests that CD62L and CD 106 are positively expressed on the surface of mesenchymal stem cells (MSCs). It has been reported that both receptors can be induced by minor necrosis factor- ⃞ (TNF-α). granulocyte-colony stimulating factor (G-CSF). and vascular endothelial growth factor (VEGF) on leucocytes. However, whether these stimulations induce CD62L and CD 106 expressions on MSCs is still unknown. Thus, in the present study we investigated the effects of TNF-α. G-CSF and VEGF on CD62L and CD 160 expressions on the surface of MSCs.

Method: MSCs were isolated from rat bone marrows, and treated with different concentrations of TNF-α (0.1.1 and 10 ng/mL), G-CSF and VEGF (1.10. and 100 ng/mL) for 12 and 24 hours respectively. Then the expressions of CD62L and C'D 106 on the surface of MSCs were analyzed by flow cytometry.

Results: Immunochemistry assay showed positive CD90 but negative CD45 in the MSCs. Flow cytometry analysis suggested that TNF-α and G-CSF could induce CD62L and CD106 expressions on the surface of MSCs in a dose-dependent manner, but not in a time-dependent manner. Further, all the concentrations of VEGF had no significant effect on the CD62L and CD106 expressions.

Conclusion: CD62L and CD106 can be induced by TNF-α and G-CSF on the surface of MSCs. but not by VEGF. These findings can help improve BM-MSC migration capability and therapeutic efficiencies of MSC transplantation.

Keywords

  • CD106
  • CD62L
  • G-CSF
  • mesenchymal stem cells
  • TNF-α
Open Access

Sensitivity enhancement of nucleic acid detection by lateral flow strip test using UV crosslink method

Published Online: 04 Feb 2017
Page range: 459 - 463

Abstract

Abstract

Background: Nucleic acid lateral flow (NALF) strip test is currently a promising method in biomedical applications for point-of-care DNA detection. However, sensitivity of NALF is a major limitation when tested without amplification of the DNA sample.

Objective: This study introduces UV crosslink as an additional step to enhance sensitivity of the test strip. Methods: By applying UV exposure to the NALF platform with different irradiation energies and times, specificity test with target DNA and non-target DNA.

Results: the results revealed increasing signals of approximately 40% from all test strips compared to those without UV exposure. Furthermore, the sensitivity enhancement by UV crosslink of NALF dipstick has been shown to be independent from DNA sequences, hybridization specificity and target DNA length.

Conclusion: Data presents a new step to improve the sensitivity of NALF assay. It allows immediate visualization and quantification. There may be a potential application in other NALF platform products.

Keywords

  • Biosensor
  • gold nanoparticles
  • lateral flow
  • nanomedicine
  • strip test
  • UV crosslink
Open Access

Elevated intracellular levels of iron in host cells promotes Burkholderia pseudomallei infection

Published Online: 04 Feb 2017
Page range: 465 - 471

Abstract

Abstract

Background: Burkholderia pseudomallei is the causative agent of melioidosis. The disease is endemic in northeast Thailand. Several studies have reported the effect of iron-overloaded environment in promoting bacterial infection. However, little is known about the effect of host cell iron elevation on melioidosis.

Objective: We investigated the impact of increased host cell iron levels on B. pseudomallei infection.

Methods: HeLa and A549 cell monolayers were supplemented with ferrous sulfate (FeSO4) and ascorbic acid to increase intracellular iron levels. The iron elevated host cells were infected with B. pseudomallei and examined for plaque formation, cell invasion, intracellular survival and multinucleated giant cell (MNGC) formation and compared to bacteria infecting control cells.

Results: The ability of B. pseudomallei to form plaques in iron supplemented HeLa cells and to invade iron supplemented A549 cells was significantly higher. Furthermore, the intracellular survival of B. pseudomallei and the ability to induce MNGC formation in iron-supplemented host cells was greater than in infected control cells.

Conclusion: Elevation of iron levels in host cells promotes B. pseudomallei infection.

Keywords

  • Burkholderia pseudomallei
  • intracellular survival
  • invasion
  • iron elevation
  • virulence
Open Access

Clinical features, risk factors, and outcome of carbapenem-resistant Acinetobacter baumannii bacteremia in a Thai neonatal intensive care unit

Published Online: 04 Feb 2017
Page range: 473 - 479

Abstract

Abstract

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) infection have been increasingly observed and are associated with mortality in neonatal population.

Objective: We determined risk factors for and outcome of bacteremia caused by CRAB in neonates.

Methods: The clinical data of neonates who developed A. baumannii bacteremia from January 2005 to December 2010 were retrospectively reviewed.

Results: During the study period, 22 neonates developed A. baumannii bacteremia, 13 were CRAB at an incidence of 0.5 case/1000 patients-day. Compared with carbapenem-sensitive A. baumannii (CSAB), patients with CRAB bacteremia had lower birth weight, lower gestational age and were more often receiving mechanical ventilation at the onset of bacteremia. Most of the CSAB isolates were susceptible to cefoperazone/sulbactam (89%) and aminoglycosides (50-75%). In contrast, CRAB strains were all resistant to cephalosporins, carbapenems, quinolones, with 39% susceptible to cefoperazone/sulbactam and 8% susceptible to amikacin. Most cases of CRAB bacteremia were treated with cefoperazone/sulbactam or meropenem and in some cases, with the addition of colistin. The all cause morality rates were 54% in CRAB and 11% in CSAB bacteremia, respectively (p = 0.07).

Conclusions: Neonatal bacteremia caused by A. baumannii was not common but caused high mortality, particularly from CRAB. Lack of effective antibiotics was the major challenge in treating these patients.

Keywords

  • Acinetobacter baumannii
  • bacteremia
  • carbapenem-resistant Acinetobacter baumannii
  • colistin
  • neonates

Clinical report

Open Access

Dumbbell-shaped primary CNS lymphoma involving the hypothalamus and pituitary gland

Published Online: 04 Feb 2017
Page range: 481 - 485

Abstract

Abstract

Background: Primary central nervous system lymphoma (PCNSL) involving the hypothalamus and pituitary gland is extremely rare. Therefore, no case to our knowledge has been reported to date.

Objective: We described our findings in a 48-year-old immunocompetent man, who presented with four months progressive diabetes insipidus (DI) and two months subsequent headache.

Methods and Results: A radiological study and magnetic resonance imaging (MRI) suggested a homogeneous enhancing dumbbell-shaped lesion, 2.4⃞1.2 cm in size, involving both the hypothalamus and pituitary gland. A brain biopsy was conducted through a transnasal transsphenoidal approach, and a final histopathological diagnosis of the tumor was confirmed as diffuse large B-cell malignant lymphoma. After extensive tumor surveys, including computed tomography, MRI, ultrasound, bone marrow biopsy, lumbar puncture, and positron emission tomography (PET), no evidence of other lesions found. Subsequently, he received six cycles of intravenous highdose methotrexate-based chemotherapy followed by one cycle of whole-brain radiotherapy. The progressive DI and headache completely resolved and he was in good health 11 months later.

Conclusion: Clinicians should consider the possibility of PCNSL in non specific clinical presentations.

Keywords

  • CD20
  • dumbbell-shaped
  • methotrexate
  • primary central nervous system lymphoma
  • whole-brain radiotherapy
Open Access

Cutaneous myiasis caused by Dermatobia hominis in Thai travelers: first report in Thailand

Published Online: 04 Feb 2017
Page range: 487 - 494

Abstract

Abstract

Background: Myiasis is the infestation with fly larvae in live vertebrate hosts. The disease has not been reported in Thailand.

Method and Results: We report the first case series of cutaneous myiasis caused by Dermatobia hominis in two Thai travelers who visited Brazil. Two of five travelers were infested with D. hominis larvae. Both presented with furuncular lesions. Surgical excision was performed for both patients and the larvae were removed. They were identified as second stage of D. hominis. Sequence data of both mitochondrial and nuclear genes of the larva were similar to previous reports from Brazil.

Conclusion: With increasing travel into endemic countries of D. hominis, physician should be aware of this parasitic infestation.

Keywords

  • Dermatobia hominis
  • imported case series
  • Myiasis
  • Thailand
Open Access

Vibrio vulnificus septicemia in Thailand: A 12-year case series and report of two fatal massive rhabdomyolysis cases

Published Online: 04 Feb 2017
Page range: 495 - 502

Abstract

Abstract Background: Vibrio vulnificus infection is prevalent among tropical coastal regions and septicemia due to this bacterium is often rapidly fatal. Our review of V. vulnificus cases in Thailand included microbiological and clinical analyses which have rarely been documented. They included a rare complication of rhabdomyolysis which has never been reported in this country.

Objective: We reported a case series of V. vulnificus septicemia at a university hospital in Thailand during a 12-year period including two fatal cases with rhabdomylysis due to V. vulnificus infection.

Methods: Our case series of patients with V. vulnificus septicemia was retrospectively reviewed to determine clinical presentations, risk factors, microbiologic data, hospital courses, treatment, and outcomes.

Results: Twenty-nine patients, predominantly male, were identified. Most patients had underlying cirrhosis or related chronic liver diseases and 20 cases (69%) died rapidly. Cellulitis and necrotizing fasciitis were common presenting symptoms. Consumption of undercooked shellfish may be a local risk factor. Inadequate surgical intervention may be related to a high mortality rate. Two fatal cases with autopsy-proven acute massive rhabdomyolysis were described, which emphasized urgent appropriate management.

Conclusion: This 29-case series identified that V. vulnificus septicemia had a high mortality rate. Chronic liver diseases are known underlying factors. Acute massive rhabdomyolysis is very rare as a fatal complication of V. vulnificus infection.

Keywords

  • Cellulitis
  • cirrhosis
  • necrotizing fasciitis
  • rhabdomyolysis
  • septicemia
  • Vibrio vulnificus
0 Articles

Editorial

Original article

Open Access

Association of interleukin-10 polymorphism and malarial susceptibility in Pakistani population

Published Online: 04 Feb 2017
Page range: 337 - 342

Abstract

Abstract

Background: Malaria is a leading cause of morbidity and mortality worldwide resulting in approximately 350 to 500 million clinical cases and up to two million deaths. In Pakistan, 1.5 million cases of malaria are reported annually. The genetic factors of both host and pathogen are related to the severity of the disease. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that can play a key role in plasmodium falciparum infection. Variations in IL-10 production are genetically related to polymorphisms within the IL-10 promoter region.

Objective:We investigated the association of IL-10 gene promoter -1082 G/A, -819 C/T, and -592 C/A polymorphism with malarial susceptibility in Pakistani individuals.

Methods: Ninety malarial patients and 99 healthy control subjects were enrolled. IL-10 genotyping was performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Results: There was no significant difference observed in inheritance pattern of studied single nucleotide polymorphisms. All the alleles, genotypes, and haplotypes had almost similar frequencies among diseased and healthy control groups. IL-10 -1,082 homozygous G was comparatively higher in healthy subjects but difference was not statistically significant.

Conclusion: We have found no significant association between IL-10 promoter polymorphism and plasmodium falciparum infection in Pakistan. Our result from Pakistani population confirm previous association in studies from Thailand, Gambia, Republic of Mali, Tanzania, and contradict one from Kenyan population.

Keywords

  • IL-10
  • malaria
  • polymorphism
  • susceptibility
Open Access

Effect of nicotine on the release of lactate dehydrogenase and the production of tumor necrosis factor-α of cultured macrophage

Published Online: 04 Feb 2017
Page range: 343 - 350

Abstract

Abstract

Background: Nicotine can affect the development of Atherosclerosis (AS). Monocytes/macrophages are the important cells hi the AS lesions.

Objective: We studied the mechanisms of smoking on AS. The effects of nicotine on macrophage were investigated hi this study.

Methods: Different concentration of nicotine (6 × 10-9~-5 mol/L), different incubation time (3, 6, 9, 12, 18, and 24 horn s) and 7 β-hydroxycholesterol (50 μg ml) were schemed in this study. After exposure of macrophage to those different conditions, lactate dehydrogenase (LDH) activity and tumor necrosis factor-⃞ (TNF-α) content in the supernatant were assayed.

Results: Nicotine (6 × 10-9mol/L~-6×10-5mol/L) treatment resulted in a marked reduction of LDH in the supernatant (131,0±9.6 U/L. 129.7±6.2 U/L, 129.4±5.3 U/L, 134.2±8.4 U/L, and 138.3+9.7 U/L vs. 151.3+8.1 U/L, p <0.05 respectively, q-test). The same change trend was seen when co-treated with 7β-hydroxycholestrol and nicotine (135.7±7.6U/L, 135.6±6.6U/L, 136.1±6.7 U/L, 142.9±4.5 U/L, and 146.4±4.4 U/L vs. 152.4⃞6.2U/L, P<0.05 respectively, q-test). The peak effects occurred at the nicotine concentration of 6 × 10-7mol/L and the first 18-hours incubation. Nicotine (6 ×10-9mol/L~6 × 10-6mol L) treatment result in the increase of TNF-α in the supernatant (0.28±0.06 ng/mL, 0.32±0.05 ng/mL, 0.40±0.07 ng/mL. and 0.30±0.08 ng/mL vs. 0.17±0.05 ng/mL, p <0.05 respectively, q-test). Nicotine (6 × 10-5mol/L) treatment have no significant hicrease compared to the control group (0.21±0.08 ng/mL vs. 0.17+0.05 ng/mL, p >0.05, q-test). The peak effects occurred at the nicothie concentration of 6 × 10-7mol/L.

Conclusions: Nicotine can produce the beneficial effect on macrophage. Nicotine treatment can activate macrophage to produce TNF-α. Thus, nicotine can be a mechanism on the development of atherosclerosis.

Keywords

  • Lactate dehydrogenase
  • macrophage
  • nicotine
  • tumor necrosis factor-α
Open Access

Imatinib regulates the alternative pre-mRNA splicing of Bcl-x in K562 cells

Published Online: 04 Feb 2017
Page range: 351 - 359

Abstract

Abstract

Background: The alternative splicing of Bcl-x generates the proapoptotic Bcl-xs protein and the antiapoptotic variant Bcl-xl. Previous studies have demonstrated that some chemotherapeutic agents such as emetine, staurosporine, and epigallocatechin gallate (EGCG) in combination with ibuprofen significantly altered the ratio of the Bcl-x variants Bcl-xs/Bcl-xl in various cell lines, suggesting Bcl-x splicing might be affected by the exogenous stimuli.

Objective: We investigated the regulative role of imatinib in the alternative pre-mRNA splicing of Bcl-x in K562 cells and the related mechanism.

Methods: Cell proliferation was measured using WST assay kit. Cell apoptosis was assayed using an Annexin V-FITC Apoptosis Detection Kit. RT-PCR and western blot assay was used to analyze the mRNA and protein level of alternative splicing of exon 2 in the Bcl-x gene respectively.

Results: Imatinib regulated the alternative splicing in the Bcl-x gene in the K562 cells. In addition, we found that hydroxyurea, another agent for the therapy of CML, could enhance the effect of imatinib on the ratio of the Bcl-xl/Bcl-xs. Moreover, the induction of alternative splicing was correlated with protein phosphatase 1 (PP1). Alternatively, pretreatment with calyculin efficiently blocked imatinib-induced alternative splcing in the K562 cells compared with okadaic acid, which showed an important role of PP1 in regulating imatinib-induced splicing.

Conclusion: Imatinib regulates the alternative splicing of Bcl-x in K562 cells, which may be associated with the activation of PP1.

Keywords

  • Alternative splcing
  • Bcl-x
  • chronic myelogenous leukemia
  • imatinib
  • protein phosphatase 1
Open Access

Percutaneous ipsilateral portal vein embolization using histoacryl glue: changing LR, resectibility rate and complications

Published Online: 04 Feb 2017
Page range: 361 - 367

Abstract

Abstract

Background: Liver resection has been the main strategy for treating either primary or secondary liver cancer. However, major liver resection may lead to postoperative liver failure. Portal vein embolization (PVE) is a procedure to induce hypertrophy of a liver remnant (LR) before major resection surgery. There are many variations in procedural techniques, with different advantages and disadvantages.

Objective: We studied change in liver remnant volume, resectibility rate, and complications after percutaneous ipsilateral portal vein embolization (PVE) using histoacryl glue.

Methods: Clinical data of 25 patients who underwent ipsilateral PVE were reviewed. Eighteen patients who had pre- and post- CT studies had total liver volumes (TLV) and LR volumes determined before and after the procedure using MDCT volumetry. Complications and respectability rates were recorded.

Results: All 18 patients who had pre-CT and post-CT studies had increased LR volumes. The mean of LR volumes before and after ipsilateral PVE were calculated at about 449 ml and 586 ml, which were statistically significant (p <0.001). The mean enlargement of LR was 30% (range 4 to 120%). There were no deaths or serious complications. The resectabilty rate was 76%.

Conclusion: Percutaneous transhepatic ipsilateral PVE could increase the LR volumes before major hepatic resection. There were no significant complications in our study group.

Keywords

  • Histoacryl glue
  • ipsilateral approach
  • liver cancer treatment
  • liver remnant
  • portal vein embolization
Open Access

Elevated adiponectin is associated with poor outcome in children with biliary atresia

Published Online: 04 Feb 2017
Page range: 369 - 376

Abstract

Abstract

Background: Biliary atresia (BA) is a severe neonatal liver disease characterized by progressive fibrosclerotic obliteration of the extrahepatic biliary tree.

Objective: We compared serum adiponectin in post Kasai BA patients with healthy controls and associate adiponectin with clinical outcomes of BA patients.

Methods: One hundred and six postoperative BA patients and 40 controls were recruited in this study. BA patients were categorized into two groups based on their serum total bilirubin (TB) levels (TB<2 mg/dL, no jaundice vs. TB ≥2 mg/dL, persistent jaundice) and alanine aminotransferase (ALT) levels (ALT<45 IU/L, normal ALT vs. ALT ≥45 IU/L, elevated ALT). Serum adiponectin levels were determined by enzyme-linked immunosorbent assay.

Results: BA patients had higher serum adiponectin levels than healthy controls (172.8±90.9 vs. 93.9±53.5 ng/mL, p <0.001). Serum adiponectin levels were elevated in BA patients with jaundice compared to those without jaundice (229.6±89.0 vs. 139.7±74.5 ng/mL, p <0.001). Furthermore, BA patients with elevated ALT displayed significantly higher levels of serum adiponectin than those with normal ALT (187.2±91.8 vs. 117.6±62.8 ng/mL, p <0.001). Additionally, BA patients with portal hypertension had substantially higher serum adiponectin than those without portal hypertension and a poorer clinical outcome (207.0±90.2 vs. 118.5±62.1 ng/mL, p <0.001).

Conclusions: Increased serum adiponectin was associated with a poor outcome in postoperative BA patients. Serum adiponectin might be utilized as a biochemical indicator reflecting the deterioration of liver function and poorer outcome in BA after Kasai operation.

Keywords

  • Adiponectin
  • biliary atresia
  • jaundice
  • liver fibrosis
  • portal hypertension
Open Access

Antiosteoporotic effect of sequential extracts and freezedried juice of Cissus quadrangularis L. in ovariectomized mice

Published Online: 04 Feb 2017
Page range: 377 - 384

Abstract

Abstract

Background: Osteoporosis becomes a major health problem in aging populations, and this disease increases the risk of bone fractures, leading to disability and mortality. Cissus quadrangularis L. (CQ) has been reported to have beneficial effects on bone metabolism; however, there has been no investigation to identify the active compounds responsible for this activity.

Objective: Sequential extracts (hexane, dichloromethane, ethanol, and water) and freeze-dried CQ juice were investigated to determine their effects on bone metabolism in an ovariectomized (ovx) mouse model.

Methods: Six-week-old ICR mice were divided into eight groups: sham-operated, ovx-control, estradiol (E2)- treated and five CQ-treated ovx-mouse groups (n = 3). The CQ extracts were orally administered at a dose equivalent to 5g of crude powder/kg/day for 8 weeks. Bone mineral densities (BMD) of the femur and tibia, serum levels of osteocalcin (bone formation marker) and TRAP5b (bone resorption marker), and histomorphological change of lumbar spine were determined at the end of the experiment.

Results: The BMD of the femur and tibia in the hexane-treated group were elevated to the same level as those of sham-operated group. This BMDs correlated with restoration of the trabecular bone of the lumbar spine, which was only observed in the hexane-treated group. These results were also supported by the lowest serum levels of osteocalcin and TRAP5b observed in this group, compared to the ovx-control and E2-treated groups, representing a decrease in the bone turnover rate. Neither signs of abnormality nor pathological changes of internal organs were observed after the experiment.

Conclusion: The hexane extract possessed antiosteoporotic activity in ovariectomized mice without any toxicity throughout the experiment. Therefore, the hexane extract is the most interesting for further bioassay-guided purification of pharmacologically active compounds.

Keywords

  • Bone mineral density
  • medicinal plant
  • osteocalcin
  • osteoporosis
  • TRAP5b
  • Vitaceae
Open Access

Altered phosphorylation of mitogen-activated protein kinases in dorsal root ganglia and sciatic nerve of rats with cisplatin-induced neuropathy

Published Online: 04 Feb 2017
Page range: 397 - 411

Abstract

Abstract

Background: Peripheral neuropathy is a major side effect of cisplatin. Cisplatin preferentially accumulates in the dorsal root ganglia (DRG) and causes neuronal apoptosis. In vitro studies have implicated mitogenactivated protein kinases (MAPKs) in cisplatin-induced apoptosis. However, this has not been confirmed in vivo.

Objective: We studied the phosphorylation of MAPKs, ERK, JNK, and p38, in the DRG and sciatic nerve of rats treated with cisplatin, and correlated it with the neuropathic abnormalities.

Methods: Cisplatin 2 mg/kg was intraperitoneally injected in rats twice a week for five consecutive weeks. Neuropathy was assessed by measuring hind-paw thermal and mechanical thresholds, sciatic motor nerve conduction velocity (MNCV) and morphometric evaluation of DRG and sciatic nerve at various time points after the start of cisplatin treatment. Western blot analysis was done to determine the ratio of phosphorylated to total forms of MAPKs in the DRG and sciatic nerve.

Results: Cisplatin induced transient thermal hypoalgesia, late reduction in MNCV and histopathological abnormalities of DRG and sciatic nerve indicating the neuropathy. ERK was activated in the nerve and DRG in the eighth and twelfth weeks, respectively. Transient activation of JNK in the nerve and DRG was observed only in the first week. At the same time point to JNK, p38 was temporarily inhibited in the DRG. Late activation of ERK was correlated with the presence of pathological changes, suggesting the possible role of ERK in these abnormalities. No correlation between MAPKs and functional abnormalities was observed.

Conclusion: MAPK ERK might play a role in cisplatin-induced structural alterations in the DRG and sciatic nerve and can be the therapeutic target. However, to prove this hypothesis, future studies using the ERK inhibitor must be done.

Keywords

  • Cisplatin
  • dorsal root ganglia
  • MAPK
  • neuropathy
  • sciatic nerve
Open Access

Effect of xanthoxylin on melanin content and melanogenic protein expression in B16F10 melanoma

Published Online: 04 Feb 2017
Page range: 413 - 422

Abstract

Abstract

Background: Reduced production of melanin and decreased or absence of melanocytes leads to various hypopigmentation disorders. Melanin synthesis is regulated by melanogenic proteins such as tyrosinase, tyrosinase-related protein 1 (TRP-1) and tyrosinase-related protein 2 (TRP -2), as well as their transcription factors.

Objectives: This study elucidated the effects of xanthoxylin on melanin content, dendriticity, melanogenic protein expression and its signal transduction pathways in mouse B16F10 melanoma cells (B16F10 cells).

Methods: Melanin production of B16F10 cells was measured by using a melanin content assay. The effect of xanthoxylin on the dendriticity of B16F10 cells was determined by a melanocyte dendricity assay. RT-PCR was used to investigate the effects of xanthoxylin on the melanogenic protein expression.

Results: We found that xanthoxylin increased melanin production, number of dendrites, tyrosinase, and microphthalmia-associated transcription factor (MITF) expression in cultured B16F10 cells. In addition, PKA and PKC inhibitor decreased melanin production, tyrosinase, and MITF expression in xanthoxylin-treated cells. However, xanthoxylin did not inhibit TRP-1 and TRP-2 expression.

Conclusion: These results indicated that xanthoxylin induces melanogenesis mainly via cAMP-mediated PKA activation. Other signaling pathways may also play a role in xanthoxylin-induced melanogenesis.

Keywords

  • Melanocyte
  • melanin
  • xanthoxylin

Brief communication (Original)

Open Access

Endorsement and implementation of high impact factor medical journals on the International Committee of Medical Journal Editors (ICMJE) policy of mandatory clinical trial registration

Published Online: 04 Feb 2017
Page range: 423 - 427

Abstract

Abstract

Objective: We determined the proportion of highest impact factor journals that follows the ICMJE policy of clinical trial registration and identified factors associated with policy implementation.

Study design and setting: Ten highest impact factor journals from ten specialties were identified from the 2009 Journal Citation Reports. Instructions for authors were reviewed for the statements regarding the trial registration. If the registration policy was mentioned in the instructions, the published articles were assessed to determine if the policy was actually implemented. The publishers, membership in Committee on Publication Ethics, journal vintage, etc., were analyzed for association with the policy implementation.

Results: Of 87 relevant journals, 58.6% endorsed the policy and 35.6% strictly implemented it. Factors for journals associated with strict clinical trial registration policy implementation were Internal Medicine specialty (OR 19.19; 95%CI: 2.21, 166.50; p = 0.007), ICMJE’s URM followers (OR 7.14; 95%CI: 2.62, 19.46; p <0.001), longer years of publication (OR for every 10 year 1.31; 95%CI: 1.16, 1.49; p = 0.001), and higher impact factors (OR for every 1 JIF 1.70; 95%CI: 1.25, 2.32; p = 0.001).

Conclusion: Only one third of the highest impact factor journals strictly implemented ICMJE policy. Associated factors were identified.

Keywords

  • Associated factors
  • clinical trial registration
  • endorsement
  • impact factor
  • implementation
  • policy
Open Access

Safety of equine rabies immunoglobulin injection into fingers and toes

Published Online: 04 Feb 2017
Page range: 429 - 432

Abstract

Abstract

Background: International guidelines recommend infiltration of Rabies Immunoglobulin (RIG) into and around animal bite wounds in category III potential rabies exposures. This is followed by vaccination with an approved tissue culture rabies vaccine.

Objective: We assessed the feasibility and safety of injecting Equine Rabies Immunoglobulin (ERIG) into anatomical sites with less space for expansion. Methods: A prospective study on 195 patients having category III animal bites over fingers, toes, nose, ear lobule, and eyelids was carried out at the Anti-Rabies Clinic of Maharaja Krushna Chandra Gajapati Medical College, Berhampur, Orissa, India. All patients received Equine Rabies Immunoglobulin (ERIG).

Results: No major side effects were observed. Minor side effects included induration (67.1%), pain (53.8%), and pruritus (29.2%). No compartment syndrome was seen.

Conclusion: Injecting ERIG into and around bite wounds following WHO and US-CDC guidelines in areas where no ample space is available, such as fingers, is a safe procedure.

Keywords

  • Equine rabies immunoglobulin
  • finger injury
  • rabies
Open Access

Endoplasmic reticulum protein ERp29 and doxorubicininduced toxicity in H9c2 cardiomyocytes: a comparative proteomics analysis

Published Online: 04 Feb 2017
Page range: 433 - 437

Abstract

Abstract

Background: Doxorubicin has been widely used to treat many cancers. It also induces cumulative and delayed cardiomyopathy. New biological markers to predict cardiac toxicity is needed.

Objectives: We identified novel markers and potential therapeutic targets of doxorubicin (DOX)-induced cardiac toxicity by proteomics approach.

Methods: The protein profiling of H9c2 cells in response to DOX at an apoptosis-induced concentration (0.5⃞M) were compared by two-dimensional electrophoresis (2-DE) and mass spectrometry.

Results: A total of nine differently expressed proteins were identified including six up-regulated and three downregulated proteins. We further confirmed the expression of two down-regulated proteins, prohibitin and endoplasmic reticulum protein ERp29 (ERp29), decreased in response to DOX induction by Western-blot, and over-expression of ERp29 also partially recovered the MTT reduction.

Conclusion: We first identified ERp29 and prohibitin as novel markers for DOX toxicity, and ERp29 might be a candidate target to develop novel therapeutic strategies to alleviate adverse effects of doxorubicin-based chemotherapies.

Keywords

  • Apoptosis
  • cardiac toxicity
  • doxorubicin
  • ERp29
  • proteomics
Open Access

The expression of opticin in vitreous body and retina of diabetes mellitus rats

Published Online: 04 Feb 2017
Page range: 439 - 444

Abstract

Abstract

Background: Diabetic retinopathy is a common complication of diabetes mellitus. Opcitin is a glycoprotein present in the vitreous body. Its role in diabetic retinopathy needs to be further defined.

Objective: Investigate and compare the mRNA and protein levels of opticin in vitreous body and retina in normal and diabetic rats.

Methods: Twenty-four male Sprague-Dawley (SD) rats were randomly divided into two groups (12/group), a streptozocin-induced diabetes (STZ) group and a control group. In the STZ group, 1% sterile STZ solution was injected into the rats intraperitonally (60mg/kg). An equal volume of sodium citrate buffer solution was administrated in the rats from the control group. The rats were sacrificed one month after various treatments. The eye bodies of three rats from each group were removed and fixed with 4% paraformaldehydeion for the following pathological analysis. Meanwhile, the vitreous bodies and retina of the other nine rats from each group were removed for the real-time PCR, immunohistochemistry, and western blot assays.

Results: The mRNA level of opticin in the vitreous body of diabetes mellitus (DM) rats was 5.66% of that of the control ones (p <0.01). The expression of opticin mRNA in retina of DM rats was 9.28% of that of the control ones (p <0.01). In addition, opticin protein was expressed in the vitreous body and retina of the normal rats, whereas it was negative in the DM ones.

Conclusions: The opticin expression in vitreous body and retina of diabetes rats was significantly decreased or even disappeared, which may suggest a key role of opticin in the development of diabetic retinopathy.

Keywords

  • Diabetic retinopathy
  • opticin
  • rat
Open Access

Acute cadmium exposure augments MMP-9 secretion and disturbs MMP-9/TIMP-1 balance

Published Online: 04 Feb 2017
Page range: 445 - 451

Abstract

Abstract

Background: Cadmium (Cd) is an extremely toxic metal commonly found in industrial work places, a food contaminant and a major component of cigarette smoke. Tobacco smoke and Cd inhalation result in alveolar inflammation, accumulation of immune cells and proteases/anti-proteases imbalance associated with chronic obstructive pulmonary disease and emphysema.

Objectives: We studied Cd toxicity on U-937 monocytoid cells and its influence on matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor (TIMP1) levels.

Methods: U-937 cells were cultured and treated with either concentrations of 1.0, 10.0 or 50.0 μM cadmium chloride. Cytotoxicity percentages were measured by activity assay of lactate dehydrogenase released into culture medium of treated and the control cells. MMP-9 and TIMP-1 levels were determined by ELISA. Zymography technique was used to quantify MMP-9 gelatinolytic activity in culture media of U-937 cells. Alterations in MMP-9 and TIMP-1 gene expressions in response to Cd were analyzed by real-time PCR method.

Results: Cd found to be dose-dependently cytotoxic where 50.0 μM Cd significantly increased LDH leakage from the cells (p <0.05). MMP-9 levels measured by ELISA and zymography methods showed significant 44% and 48% increase, respectively, following exposure to 50.0 μM of Cd (p <0.05). Cd doses did not exert any effect on TIMP-1 levels. Alteration in MMP-9/TIMP-1 genes expressions in response to Cd found to be below a half fold increase for all doses which were not statistically significant.

Conclusion: These results suggest that Cd has direct detrimental effects on cell viability, MMPs activity and protease/anti-protease balance which may contribute to alveolar wall destruction and pulmonary diseases.

Keywords

  • Cadmium
  • MMP-9
  • monocytic cells
  • TIMP-1
Open Access

TNF-α and G-CSF induce CD62L and CD106 expressions on rat bone marrow-derived MSCs

Published Online: 04 Feb 2017
Page range: 453 - 458

Abstract

Abstract

Background: Accumulating evidence suggests that CD62L and CD 106 are positively expressed on the surface of mesenchymal stem cells (MSCs). It has been reported that both receptors can be induced by minor necrosis factor- ⃞ (TNF-α). granulocyte-colony stimulating factor (G-CSF). and vascular endothelial growth factor (VEGF) on leucocytes. However, whether these stimulations induce CD62L and CD 106 expressions on MSCs is still unknown. Thus, in the present study we investigated the effects of TNF-α. G-CSF and VEGF on CD62L and CD 160 expressions on the surface of MSCs.

Method: MSCs were isolated from rat bone marrows, and treated with different concentrations of TNF-α (0.1.1 and 10 ng/mL), G-CSF and VEGF (1.10. and 100 ng/mL) for 12 and 24 hours respectively. Then the expressions of CD62L and C'D 106 on the surface of MSCs were analyzed by flow cytometry.

Results: Immunochemistry assay showed positive CD90 but negative CD45 in the MSCs. Flow cytometry analysis suggested that TNF-α and G-CSF could induce CD62L and CD106 expressions on the surface of MSCs in a dose-dependent manner, but not in a time-dependent manner. Further, all the concentrations of VEGF had no significant effect on the CD62L and CD106 expressions.

Conclusion: CD62L and CD106 can be induced by TNF-α and G-CSF on the surface of MSCs. but not by VEGF. These findings can help improve BM-MSC migration capability and therapeutic efficiencies of MSC transplantation.

Keywords

  • CD106
  • CD62L
  • G-CSF
  • mesenchymal stem cells
  • TNF-α
Open Access

Sensitivity enhancement of nucleic acid detection by lateral flow strip test using UV crosslink method

Published Online: 04 Feb 2017
Page range: 459 - 463

Abstract

Abstract

Background: Nucleic acid lateral flow (NALF) strip test is currently a promising method in biomedical applications for point-of-care DNA detection. However, sensitivity of NALF is a major limitation when tested without amplification of the DNA sample.

Objective: This study introduces UV crosslink as an additional step to enhance sensitivity of the test strip. Methods: By applying UV exposure to the NALF platform with different irradiation energies and times, specificity test with target DNA and non-target DNA.

Results: the results revealed increasing signals of approximately 40% from all test strips compared to those without UV exposure. Furthermore, the sensitivity enhancement by UV crosslink of NALF dipstick has been shown to be independent from DNA sequences, hybridization specificity and target DNA length.

Conclusion: Data presents a new step to improve the sensitivity of NALF assay. It allows immediate visualization and quantification. There may be a potential application in other NALF platform products.

Keywords

  • Biosensor
  • gold nanoparticles
  • lateral flow
  • nanomedicine
  • strip test
  • UV crosslink
Open Access

Elevated intracellular levels of iron in host cells promotes Burkholderia pseudomallei infection

Published Online: 04 Feb 2017
Page range: 465 - 471

Abstract

Abstract

Background: Burkholderia pseudomallei is the causative agent of melioidosis. The disease is endemic in northeast Thailand. Several studies have reported the effect of iron-overloaded environment in promoting bacterial infection. However, little is known about the effect of host cell iron elevation on melioidosis.

Objective: We investigated the impact of increased host cell iron levels on B. pseudomallei infection.

Methods: HeLa and A549 cell monolayers were supplemented with ferrous sulfate (FeSO4) and ascorbic acid to increase intracellular iron levels. The iron elevated host cells were infected with B. pseudomallei and examined for plaque formation, cell invasion, intracellular survival and multinucleated giant cell (MNGC) formation and compared to bacteria infecting control cells.

Results: The ability of B. pseudomallei to form plaques in iron supplemented HeLa cells and to invade iron supplemented A549 cells was significantly higher. Furthermore, the intracellular survival of B. pseudomallei and the ability to induce MNGC formation in iron-supplemented host cells was greater than in infected control cells.

Conclusion: Elevation of iron levels in host cells promotes B. pseudomallei infection.

Keywords

  • Burkholderia pseudomallei
  • intracellular survival
  • invasion
  • iron elevation
  • virulence
Open Access

Clinical features, risk factors, and outcome of carbapenem-resistant Acinetobacter baumannii bacteremia in a Thai neonatal intensive care unit

Published Online: 04 Feb 2017
Page range: 473 - 479

Abstract

Abstract

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) infection have been increasingly observed and are associated with mortality in neonatal population.

Objective: We determined risk factors for and outcome of bacteremia caused by CRAB in neonates.

Methods: The clinical data of neonates who developed A. baumannii bacteremia from January 2005 to December 2010 were retrospectively reviewed.

Results: During the study period, 22 neonates developed A. baumannii bacteremia, 13 were CRAB at an incidence of 0.5 case/1000 patients-day. Compared with carbapenem-sensitive A. baumannii (CSAB), patients with CRAB bacteremia had lower birth weight, lower gestational age and were more often receiving mechanical ventilation at the onset of bacteremia. Most of the CSAB isolates were susceptible to cefoperazone/sulbactam (89%) and aminoglycosides (50-75%). In contrast, CRAB strains were all resistant to cephalosporins, carbapenems, quinolones, with 39% susceptible to cefoperazone/sulbactam and 8% susceptible to amikacin. Most cases of CRAB bacteremia were treated with cefoperazone/sulbactam or meropenem and in some cases, with the addition of colistin. The all cause morality rates were 54% in CRAB and 11% in CSAB bacteremia, respectively (p = 0.07).

Conclusions: Neonatal bacteremia caused by A. baumannii was not common but caused high mortality, particularly from CRAB. Lack of effective antibiotics was the major challenge in treating these patients.

Keywords

  • Acinetobacter baumannii
  • bacteremia
  • carbapenem-resistant Acinetobacter baumannii
  • colistin
  • neonates

Clinical report

Open Access

Dumbbell-shaped primary CNS lymphoma involving the hypothalamus and pituitary gland

Published Online: 04 Feb 2017
Page range: 481 - 485

Abstract

Abstract

Background: Primary central nervous system lymphoma (PCNSL) involving the hypothalamus and pituitary gland is extremely rare. Therefore, no case to our knowledge has been reported to date.

Objective: We described our findings in a 48-year-old immunocompetent man, who presented with four months progressive diabetes insipidus (DI) and two months subsequent headache.

Methods and Results: A radiological study and magnetic resonance imaging (MRI) suggested a homogeneous enhancing dumbbell-shaped lesion, 2.4⃞1.2 cm in size, involving both the hypothalamus and pituitary gland. A brain biopsy was conducted through a transnasal transsphenoidal approach, and a final histopathological diagnosis of the tumor was confirmed as diffuse large B-cell malignant lymphoma. After extensive tumor surveys, including computed tomography, MRI, ultrasound, bone marrow biopsy, lumbar puncture, and positron emission tomography (PET), no evidence of other lesions found. Subsequently, he received six cycles of intravenous highdose methotrexate-based chemotherapy followed by one cycle of whole-brain radiotherapy. The progressive DI and headache completely resolved and he was in good health 11 months later.

Conclusion: Clinicians should consider the possibility of PCNSL in non specific clinical presentations.

Keywords

  • CD20
  • dumbbell-shaped
  • methotrexate
  • primary central nervous system lymphoma
  • whole-brain radiotherapy
Open Access

Cutaneous myiasis caused by Dermatobia hominis in Thai travelers: first report in Thailand

Published Online: 04 Feb 2017
Page range: 487 - 494

Abstract

Abstract

Background: Myiasis is the infestation with fly larvae in live vertebrate hosts. The disease has not been reported in Thailand.

Method and Results: We report the first case series of cutaneous myiasis caused by Dermatobia hominis in two Thai travelers who visited Brazil. Two of five travelers were infested with D. hominis larvae. Both presented with furuncular lesions. Surgical excision was performed for both patients and the larvae were removed. They were identified as second stage of D. hominis. Sequence data of both mitochondrial and nuclear genes of the larva were similar to previous reports from Brazil.

Conclusion: With increasing travel into endemic countries of D. hominis, physician should be aware of this parasitic infestation.

Keywords

  • Dermatobia hominis
  • imported case series
  • Myiasis
  • Thailand
Open Access

Vibrio vulnificus septicemia in Thailand: A 12-year case series and report of two fatal massive rhabdomyolysis cases

Published Online: 04 Feb 2017
Page range: 495 - 502

Abstract

Abstract Background: Vibrio vulnificus infection is prevalent among tropical coastal regions and septicemia due to this bacterium is often rapidly fatal. Our review of V. vulnificus cases in Thailand included microbiological and clinical analyses which have rarely been documented. They included a rare complication of rhabdomyolysis which has never been reported in this country.

Objective: We reported a case series of V. vulnificus septicemia at a university hospital in Thailand during a 12-year period including two fatal cases with rhabdomylysis due to V. vulnificus infection.

Methods: Our case series of patients with V. vulnificus septicemia was retrospectively reviewed to determine clinical presentations, risk factors, microbiologic data, hospital courses, treatment, and outcomes.

Results: Twenty-nine patients, predominantly male, were identified. Most patients had underlying cirrhosis or related chronic liver diseases and 20 cases (69%) died rapidly. Cellulitis and necrotizing fasciitis were common presenting symptoms. Consumption of undercooked shellfish may be a local risk factor. Inadequate surgical intervention may be related to a high mortality rate. Two fatal cases with autopsy-proven acute massive rhabdomyolysis were described, which emphasized urgent appropriate management.

Conclusion: This 29-case series identified that V. vulnificus septicemia had a high mortality rate. Chronic liver diseases are known underlying factors. Acute massive rhabdomyolysis is very rare as a fatal complication of V. vulnificus infection.

Keywords

  • Cellulitis
  • cirrhosis
  • necrotizing fasciitis
  • rhabdomyolysis
  • septicemia
  • Vibrio vulnificus